SciTech Development LLC optimizes lead anticancer agents via novel, rational modifications that enhance drug performance in vivo. 2-Aryl- lactic acids show highly selective activity against solid tumors and novel, specific inhibition of topoisomerase II-beta. Their stereochemistry reportedly affects therapeutic index and drug disposition, attracting SciTech's interest. At AACR-NCI-EORTC 1999, a poster showed rodents, dogs, and primates rapidly converting the S stereoisomer of a NCI clinical candidate into R In vitro, bone marrow neutrophil progenitors tolerated the S isomer better than R. Hence, the goal of this SBIR: development of novel S isomers of 2-aryl-lactic acids refractory to stereoinversion in vivo and thereby better anticancer agents. SciTech proposes three chemical synthetic strategies for stabilizing 2(S)-aryl-lactic acid anticancer agents. Phase I will demonstrate feasibility and assess prototype structures using in vitro tests for human metabolism, human bone marrow safety, and solid tumor efficacy. In Phase II, analogs will be synthesized using these strategies, required to pass this in vitro testing and in vivo testing for stabilized stereochemistry, and clinical candidates prioritized by efficacy in human tumor xenograft models. This research could lead to effective solid tumor agents and also enhance the drug being developed by the NCI. PROPOSED COMMERCIAL APPLICATIONS: 2-Aryl-lactic acid anticancer agents are highly active against a broad panel of solid tumors in preclinical models including tumors that represent major market opportunities for highly active drugs: cancers of the breast, colon, prostate, and pancreas. The proposed structures stabilize the most active stereoisomers and create novel compounds not covered by existing patents in this area.